Table 3.

Molecular defects in the ESR1 gene, in vitro activity of mutants, and clinical phenotype in published 46, XY subjects with estrogen resistance due to ESR1-mutations.

Gene Mutations	Description	Functional analysis	Phenotype	References
c.[469C>T];[469C>T]	p.Arg157Ter	Not determined (ND); however, the protein would be severely truncated lacking DNA binding and substrate binding domains.	At Birth: Normal male genitalia, bilateral descended testes. At 28 years: Tall stature, genu valgum. High serum estrogens and gonadotropins. Normal sperm density. Severely undermineralized skeleton.	(72)
c.[1181G>A];[1181G>A]	p.Arg394His	Strongly reduced transcriptional activity and inability to securely anchor the activating hormone, estradiol, compared with wild-type ERα.	At 18 years: Marked delayed bone maturation. Tanner stage I gonadal development with a cryptorchid right testis. Hypoplastic left testis. High serum basal 17β estradiol and gonadotropin levels, and low testosterone levels.	(73)